BeOne Medicines Reports Phase 3 HERIZON-GEA Results Published in NEJM and Featured at ASCO 2026
BeOne Medicines has announced the publication and upcoming presentation of significant new clinical data from the HERIZON-GEA-01 trial evaluating ZIIHERA in combination with chemotherapy, with and without TEVIMBRA, in patients with advanced or metastatic HER2-positive gastroesophageal adenocarcinoma (GEA). The findings, published in The New England Journal of Medicine and scheduled for oral presentation at the ASCO Annual Meeting 2026 in Chicago, highlight what investigators describe as potentially practice-changing improvements in survival outcomes for patients with this aggressive form of cancer.
The HERIZON-GEA-01 study compared two investigational treatment regimens — zanidatamab plus chemotherapy and zanidatamab combined with tislelizumab and chemotherapy — against a control regimen consisting of trastuzumab plus chemotherapy, which currently represents a standard first-line treatment approach for HER2-positive advanced gastroesophageal adenocarcinoma.
Gastroesophageal adenocarcinoma is a highly aggressive cancer affecting the stomach and esophagus, and HER2-positive disease represents a biologically distinct subset characterized by overexpression of the HER2 protein. BeOne Although HER2-targeted therapies such as trastuzumab have improved outcomes for some patients, prognosis remains poor for many individuals with advanced or metastatic disease, creating continued demand for more effective treatment strategies.
According to the results reported in the study, the triplet combination of ZIIHERA, TEVIMBRA, and chemotherapy demonstrated statistically significant and clinically meaningful improvements in overall survival, progression-free survival, and duration of response compared with the trastuzumab-based control regimen.
Investigators reported that patients receiving the ZIIHERA plus TEVIMBRA and chemotherapy combination achieved a median overall survival of 26.4 months. BeOne By comparison, median overall survival reached 24.4 months among patients treated with ZIIHERA plus chemotherapy without TEVIMBRA and 19.2 months in the control arm receiving trastuzumab plus chemotherapy.
The study also demonstrated substantial improvements in progression-free survival, a measure reflecting the length of time patients live without disease worsening. Both ZIIHERA-containing treatment arms achieved a median progression-free survival of 12.4 months, representing a clinically meaningful improvement compared with the control regimen.
In addition, researchers observed longer-lasting treatment responses among patients receiving the investigational combinations. Median duration of response reached 20.7 months in the triplet therapy arm that included TEVIMBRA, compared with 14.3 months for ZIIHERA plus chemotherapy and 8.3 months for the trastuzumab-based control treatment.
Sun Young Rha, Professor of BeOne Medical Oncology at the Yonsei Cancer Center within Yonsei University College of Medicine, served as senior author of the New England Journal of Medicine manuscript and first author of the ASCO presentation abstract.
Rha stated that the results provide important new evidence supporting the addition of tislelizumab to zanidatamab plus chemotherapy in HER2-positive gastroesophageal adenocarcinoma. BeOne She emphasized that the regimen demonstrated meaningful survival benefits, including among patients whose tumors had low or negative PD-L1 expression, a population that often derives less benefit from immunotherapy-based treatment approaches.
According to Rha, the findings suggest the combination could emerge as a significant new treatment option for patients facing limited therapeutic alternatives in advanced HER2-positive gastroesophageal cancer.
The BeOne ASCO 2026 presentation will include additional subgroup analyses examining outcomes according to PD-L1 status. Researchers reported that after 26 months of follow-up, the triplet regimen demonstrated improved progression-free survival and overall survival in both PD-L1-positive and PD-L1-negative patients compared with the control arm.
In patients with PD-L1 tumor area positivity (TAP) scores below 1%, median overall survival reached 29.7 months for those treated with ZIIHERA plus TEVIMBRA and chemotherapy, compared with 15.8 months in the control group. Among PD-L1-positive patients with TAP scores of at least 1%, median overall survival was 26.4 months in the investigational triplet arm versus 21.2 months in the control arm.
Researchers noted that the findings remained consistent across different PD-L1 assessment methods, including tumor area positivity and combined positive score evaluations.
The progression-free survival data also showed substantial improvements in both patient populations. Among PD-L1-negative patients, median progression-free survival reached 18.5 months with the ZIIHERA plus TEVIMBRA regimen, compared with 7.9 months in the control arm. In PD-L1-positive patients, median progression-free survival measured 11.3 months with the triplet therapy versus 8.3 months with trastuzumab plus chemotherapy.
Geoffrey Ku, Associate BeOne Attending Physician on the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center, described the study as practice-changing and stated that zanidatamab demonstrated clear superiority over trastuzumab while maintaining a manageable safety profile in HER2-positive gastroesophageal adenocarcinoma.
Ku also highlighted the contribution of tislelizumab to the prolongation of overall survival and durability of treatment responses. He noted that the observed benefits extended across both PD-L1-positive and PD-L1-negative tumors, which could broaden the applicability of the regimen if approved by regulators.
According to Ku, the combination of zanidatamab, tislelizumab, and chemotherapy has the potential to become a new standard of care for untreated metastatic or locally advanced HER2-positive gastroesophageal adenocarcinoma regardless of PD-L1 status.
Mark Lanasa, Chief Medical Officer for Solid Tumors at BeOne Medicines, stated that the publication of the HERIZON-GEA-01 results in The New England Journal of Medicine and the presentation of subgroup analyses at ASCO further strengthen the evidence supporting TEVIMBRA’s role in improving survival outcomes.
Lanasa noted that achieving a median overall survival exceeding 26 months is unprecedented in this disease setting and positions the TEVIMBRA-containing regimen as a compelling therapeutic approach for a patient population with significant unmet medical need.
Safety findings from the trial were reported to be generally consistent with the known safety profiles of HER2-targeted therapies and immunotherapies. Investigators indicated that no new safety signals were identified during the study.
Diarrhea was the most commonly observed Grade 3 or higher treatment-related adverse event. It occurred in 24.5% of patients receiving ZIIHERA plus TEVIMBRA and chemotherapy, 20.0% of patients treated with ZIIHERA plus chemotherapy, and 12.9% of patients in the trastuzumab control arm.
Researchers noted that the triplet regimen also involved the longest median treatment duration at 43.1 weeks, compared with 31 weeks for the ZIIHERA plus chemotherapy arm and 30 weeks for the control regimen. To help manage gastrointestinal toxicity, mandatory anti-diarrheal prophylaxis was implemented during the first treatment cycle.
Importantly, discontinuation rates related to drug-associated diarrhea remained relatively low across the study, occurring in 4.1% of patients in the triplet therapy arm, 1.3% in the dual therapy arm, and no patients in the control arm. Most diarrhea events occurred early during treatment.
The promising clinical findings are also influencing ongoing regulatory activities. U.S. Food and Drug Administration has accepted a supplemental Biologics License Application for TEVIMBRA and granted the application priority review status.
Additionally, the National Medical Products Administration through its Center for Drug Evaluation has accepted supplemental Biologics License Applications for both ZIIHERA and TEVIMBRA for the first-line treatment of advanced or metastatic HER2-positive gastroesophageal adenocarcinoma.
BeOne Medicines currently holds commercialization rights for ZIIHERA across Asia excluding India and Japan, as well as Australia and New Zealand. The company stated that it intends to work closely with regulatory authorities across these markets to accelerate review and potential approval processes.
The HERIZON-GEA-01 findings represent one of the most closely watched developments in HER2-positive gastrointestinal oncology and may significantly influence future treatment paradigms if regulatory approvals are secured.
About the HERIZON-GEA-01 Phase 3 Trial
HERIZON-GEA-01 (NCT05152147) is a global, randomized, open-label Phase 3 trial, conducted jointly with Jazz Pharmaceuticals, to evaluate and BeOne ompare the efficacy and safety of ZIIHERAplus chemotherapy, with and without TEVIMBRA, to the standard of care (trastuzumab plus chemotherapy) as first-line treatment for adult patients with advanced/metastatic HER2+ GEA. The trial randomized 914 patients from approximately 300 trial sites in more than 30 countries.
Patients for this trial had unresectable locally advanced, recurrent or metastatic HER2+ GEA (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISH positivity per central assessment. Patients were randomized to the three trial arms: ZIIHERAin combination with chemotherapy and TEVIMBRA; ZIIHERA in combination with chemotherapy; and trastuzumab plus chemotherapy. The trial is evaluating dual primary endpoints, PFS per blinded independent central review (BICR) and OS.
About Gastroesophageal Adenocarcinoma
Gastroesophageal adenocarcinoma (GEA), which includes cancers of the stomach, gastroesophageal junction, and esophagus, is the fifth most common cancer worldwide. Approximately 20% of GEA patients have HER2-positive disease.1,2,3, which has high morbidity and mortality, and patients are urgently in need of new treatment options. The overall prognosis for patients with GEA remains poor, with a global five-year survival rate of less than 30% for gastric cancer and about 19% for GEA.4
About ZIIHERA (zanidatamab)
ZIIHERA (zanidatamab) is a bispecific human epidermal growth factor receptor 2, or HER2-directed antibody that binds to two extracellular sites on HER2. Binding of zanidatamab with HER2 results in internalization leading to a reduction in HER2 expression of the receptor on the tumor cell surface. Zanidatamab induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.5
Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is approved in China for the treatment of patients who have unresectable, locally advanced, or metastatic HER2-high expression (IHC 3+) biliary tract cancer (BTC) and who have received prior systemic therapy.
ZIIHERA has also been granted accelerated approval in the U.S. and conditional marketing authorization in the European Union for eligible BTC patients. Zanidatamab is being developed by Jazz and BeOne under license agreements from Zymeworks, which first developed the molecule. BeOne has licensed zanidatamab from Zymeworks in Asia (excluding India and Japan), Australia and New Zealand. Jazz Pharmaceuticals has rights in all other regions.
ZIIHERA is a registered trademark of Zymeworks BC Inc.
About TEVIMBRA (tislelizumab)
TEVIMBRA is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors.
TEVIMBRA is the foundational asset of BeOne’s solid tumor portfolio and has shown potential across multiple tumor types and disease settings. The global TEVIMBRA clinical development program includes almost 15,000 patients enrolled to date in 30+ countries and regions across 71 trials, including 21 registration-enabling studies. TEVIMBRA is approved in over 50 countries, and more than 2 million patients have been treated globally.
